P1271: THE IMPACT OF CYTOMEGALOVIRUS-SPECIFIC T CELLS USAGE AS ADOPTIVE THERAPY IN PATIENTS WITH PT-CY AND TCR ΑΒ+/CD19+ CELLS DEPLETION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Anna Dmitrova, Mikhail Drokov, Tatiana Tupoleva, Dmitriy Tikhomirov, Grigoriy Efimov, Apollinariya Bogolyubova, Alexandra Maleeva, Murad Vagida, Zalina Fidarova, Evgeniy Zvonkov, Larisa Kuzmina, Elena Parovichnikova
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: A large number of reviews is devoted to affection of different types of graft-versus-host disease (GvHD) prophylaxis regimens on the reconstitution of the T-cell immunity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Association of the posttransplant cyclophosphamide (PT-CY) together with TCR αβ+/CD19+ cell depletion is associated with the deeper T cell deficiency after allo-HSCT. Cytomegalovirus (CMV) specific T lymphocytes transfusion as adoptive T cell therapy (ACT) can boost reconstitution of the CMV-specific immunity and provide long-term protection against CMV-infection. Aims: To evaluate the impact of ACT with using CMV-specific T cells on the reconstitution of CMV-specific T-cell immunity after allo-HSCT. Methods: Total 64 recipients of peripheral blood stem cells (PBSC) as the graft source after TCR αβ+/CD19+ cells depletion and PT-CY as GvHD prophylaxis were included in the analysis. Seventeen (26.5%) patients received ACT at the +30 day after the engraftment. All patients reached engraftment after allo-HSCT. Absolute count of CMV-specific T cells at +30, +90, +180 day after allo-HSCT in peripheral blood samples was estimated via flow cytometry analysis. The detection of CMV-specific T cells was performed by using tetramers formed from MHC class I monomers loaded with immunodominant epitopes of cytomegalovirus pp65 protein (HLA-A*02/NLV, HLA-B*07/TPR, HLA-B*07/RPH) and Streptavidin, R-Phycoerythrin conjugate (SAPE). We formed two groups due to the presence of the ACT after engraftment. These groups were balanced by two main factors affecting CMV-specific immunity: GvHD prophylaxis regimen and CMV-serologic status of Donor-Recipient pairs (D/ R). Results: As shown in figure 1 the absolute number of CMV-specific T cells had not significantly differed between groups before ACT (on day +30). After that on day +90 in the group with CMV-specific T cell transfusion the number of CMV-specific T cells was significantly higher compared to the group without ACT (p=0.013).Figure 1. The comparison of the absolute count of CMV-specific T cells (cell/µl) in peripheral blood samples at +30, +90, +180 day after allo-HSCT depending on the use of adoptive T cell therapy. Summary/Conclusion: Transfusion of donor CMV-specific T-lymphocytes after the engraftment from +30 day after allo-HSCT effectively boost the reconstruction of CMV-specific immunity in patients with highly aggressive GvHD prophylaxis regimens, including PT-CY and TCR αβ+/CD19+ cells depletion. Thus, tge presence of the ACT in prophylaxis protocols for management of CMV infection after allo-HSCT can accelerate virus‐specific immune reconstitution. Keywords: CMV infection, Adoptive immunotherapy, Stem cell transplant, T cell reconstitution